tbuckley/cabot-search huggingface dataset:
MEDB-77. Metastasic medulloblastoma: radiological features and its correlation with molecular subgroups and dissemination pattern
Authors: Marina Caballero Bellón, Marta Pérez-Somarriba Moreno, Cinzia Lavarino, Vicente Santa-María Lopez, Ofelia Cruz Martinez, Jordi Muchart Lopez, Andrés Morales La Madrid
Journal: Neuro-Oncology (2022)

Abstract Medulloblastoma (MB) is the most frequent malignant childhood brain tumor. Four molecular subgroups have been described (WNT, SHH, group3, group4), which are associated with a different biological profile, prognosis, specific MRI characteristics and patterns of metastatic dissemination. We aimed to determine the imaging features of the metastatic MB and its molecular subgroup and their outcomes. Retrospective single-center analytic-observational study conducted from January 2004-January 2022 in a tertiary-care center. Pediatric patients with metastatic medulloblastoma at disease onset were included. We collected epidemiological and clinical characteristics, treatment received, and outcomes. The molecular subgroup was determined by its methylation profile. MRI were reviewed by the neuroradiologist. Sixty-three patients were diagnosed, 17 (26.9%) were metastatic. The median age at diagnosis was 5.1 years (range 2.1-17.5 years), 58.8% were male. According to histopathologic classification, fifteen patients (93.8%) were classic,1 (6.3%) desmoplastic. Molecular subgroup analysis showed 2 WNT (12.5%), 1 SHH (6.3%), 3 (18.8%) group 3 (G3) and 5 (31.2%) group 4 (G4). Four patients (25%) were classified as G3/G4 and 1 (6.3%) as mixed. Five patients (29.4%) were M2 and 12 patients (70.6%) were M3 according to Chang staging system. The location in the cerebellar hemispheres was only observed in SHH patient while G3 tumors presented homogeneous contrast enhancement. All WNT, G3 and G4 were located in IV ventricle. We found no association between molecular subgroup and metastatic site (intracranial vs spinal, Fisher test, p=0.45). All patients presented with metastasis in the third ventricular infundibular recess were G4. Four patients died, all of them were G3 or G3/G4. Our results supported the literature previously reported. According to the MRI imaging features, the molecular medulloblastoma subgroups could be suggested. The presence of metastasis in the infundibular recess suggested MB group 4. However, the dissemination pattern could not be associated with any subgroup in our series.
Development and multimodal validation of a substance misuse algorithm for referral to treatment using artificial intelligence (SMART-AI): a retrospective deep learning study
Authors: Majid Afshar, Brihat Sharma, Dmitriy Dligach, Madeline Oguss, Randall Brown, Neeraj Chhabra, Hale M Thompson, Talar Markossian, Cara Joyce, Matthew M Churpek, Niranjan S Karnik
Journal: The Lancet Digital Health (2022)
An anti-inflammatory and neuroprotective biomimetic nanoplatform for repairing spinal cord injury
Authors: Xiang Gao, Zhihui Han, Cheng Huang, Huali Lei, Guangqiang Li, Lin Chen, Dandan Feng, Zijie Zhou, Qin Shi, Liang Cheng, Xiaozhong Zhou
Journal: Bioactive Materials (2022)

Spinal cord regeneration after a spinal cord injury (SCI) remains a difficult challenge due to the complicated inflammatory microenvironment and neuronal damage at the injury sites. In this study, retinoic acid (RA) and curcumin (Cur) were co-loaded with bovine serum albumin (BSA) self-assembly to obtain RA@BSA@Cur nanoparticles (NPs) for SCI treatment. Cur, as an antioxidant drug, facilitated reactive oxygen species (ROS) scavenging, and decreased the amount of inflammatory factors secreted by macrophages, while RA could enhance neurite extensions and neural differentiation. The constructed RA@BSA@Cur NPs not only induced polarization of macrophages toward pro-regenerative phenotypes and markedly reduced the inflammatory response of macrophages or microglia, but also increased neurite length in PC12 cells and neuronal differentiation of bone marrow mesenchymal stem cells, improved the differentiation of neural stem cells (NSCs) into β3-tubulin+ neurons, and reversed the pro-astrocyte differentiation effect of inflammatory cytokines on NSCs. In vivo experiments revealed that RA@BSA@Cur NPs regulated the phenotypic polarization of macrophages, inhibited the release of inflammatory mediators, promoted functional neuron regeneration and motor function, and further inhibited scar tissue formation. This study highlighted that the BSA-based biomimetic nanomaterials could be used as ROS scavengers and nerve regeneration promoters for treating SCI.
Circulating tumor cells as a biomarker for precise management in lung cancer.
Authors: Juan Chen, Qian Li, Chen-yu Xu, Ying-ying Qian, Zhen-hua Yang, Dong-sheng Chen
Journal: Journal of Clinical Oncology (2022)

e21018 Background: Circulating tumor cells (CTCs) have potential utility in various clinical application for cancer management. In this study, we evaluated whether circulating tumor cells (CTCs) provide early diagnostic information and/or precisely indication of patient response to chemotherapy. Methods: 56 patients with newly diagnosed lung cancer, 42 patients with nonmalignant pulmonary disease and 27 healthy controls were enrolled in this study. CTCs were measured at baseline in all eligible subjects and after two cycles of chemotherapy in 25 advanced lung cancer patients, with a strategy of negative enrichment combined with immunostaining-fluorescence in situ hybridization (imFISH). The receiver operating characteristic (ROC) curve was plotted to determine the sensitivity and specificity of the CTC detection for diagnosis. Kaplan-Meier curve and two-sided log-rank test were used for univariate survival analyses. Results: The number of CTCs was significantly increased in lung cancer patients, compared with benign lung disease patients and healthy controls. And it reached 87.5% sensitivity and 95.7% specificity at a cutoff value of 2 cells/3.2ml (AUC = 0.975, 95%CI, 0.953-0.998, p＜0.001).Moreover, the sensitivity of CTCs was much higher than individual or the combination of serum tumor markers, especially in the early detection of lung cancer. Twenty-five advanced lung cancer patients were subsequently followed for an average of 18.2 months (range 6-36 months) ， during which all patients experienced disease progression, and 16 patients died. A change in CTC count after two cycles of chemotherapy was highly predictive for PFS (13.5 v 8.5 months; p = 0.025) and OS (27.6 v 16.8 months; p = 0.009) in favor of a reduction in CTC number compared with an increase. Interestingly, among the patients whose post-treatment computed tomography(CT) results indicated stable disease(SD), PFS (14.0 v 8.7months; p = 0.033) and OS(25.8 v 15.9 months; p = 0.018) in patients whose CTC number decreased after two cycles of treatment were still significantly longer than those whose post-treatment CTCs number increased or unchanged. Conclusions: CTCs may act as precise biomarker for early detection and therapy monitoring that could compensate for imaging.
OTHR-30. Multidisciplinary approach to childhood cancer bio-banking improves enrollment and enables better access to diagnostic and therapeutic studies
Authors: Nataliya Zhukova, Dilru Habarakada, Caroline Drinkwater, Andrew Danks, Chris Xenos, Beena Kumar, Lauren Haddad, Paul Wood, Jason Cain, Ron Firestein, Peter Downie
Journal: Neuro-Oncology (2022)

Abstract Despite the significant progress made in the multi-modal treatment of childhood malignancies over the last four decades with a concomitantly increased cure rates, the benefit is still largely limited to patients with leukemias, lymphomas and localized non-CNS solid tumors, leaving patients with high-risk non-CNS solid tumours and most CNS malignancies with minimal advancements. More research is critical to understand what drives these cancers and to investigate the best ways to deliver curative therapies. Translational research relies on patient-derived tissue samples, animal models and cell-cultures to understand the biological, genetic, and molecular mechanisms of disease. To facilitate patient care and outcomes, it is becoming increasingly important that paediatric clinical trials include tissue availability as part of eligibility criteria, making collection and storage of patient tissue a mandate of personalised medicine and a pillar of modern paediatric cancer medicine. Monash Children’s Cancer Biobank was established in 2011. Since 2017, a total of 64 patients were diagnosed with CNS malignancies across all grades, with an overall 69% of patients’ tissues being biobanked at the time of initial diagnosis. A co-ordinated, multidisciplinary approach to biobanking is crucial to the success of tissue acquisition. Through the combination of an educational forum, regular neuro-surgical multi-disciplinary meetings, and the early involvement of medical oncology and biobank staff, with our neurosurgical and clinical pathology colleagues, as part of patient management planning, the tissue acquisition for biobanking increased from 44% to 82% over the course of 5 years. This consequently led to a 100% enrolment to tissue-enabling studies, significantly improving identification of targetable molecular lesions, enrolment onto treatment clinical trials and identification of patients with cancer predisposition syndromes.
The safety and efficacy of immune checkpoint inhibitor rechallenge after immune-related adverse events in stage IV NSCLC patients.
Authors: Mengni Guo, Ari M. Vanderwalde, Xinhua Yu, Gregory A. Vidal, Gary G. Tian, MD
Journal: Journal of Clinical Oncology (2022)

e21173 Background: Despite their anti-tumor efficacy, immune checkpoint inhibitors (ICIs) are associated with a variety of immune-related adverse events (irAEs). Grade ≥2 irAEs require ICI discontinuation. The decision to resume ICI treatment often remains challenging. Methods: We retrospectively studied 1051 adult patients with stage IV NSCLC treated with ICIs at West Cancer Center between January 2015 and December 2020. 99 (9.4%) patients with grade≥2 irAEs necessitating treatment interruption were identified. 40 patients underwent retreatment (rechallenged group), while 59 discontinued treatment (discontinued group). All patients were rechallenged with the initial ICI. Results: The baseline characteristics of patients in the two groups were similar in terms of age, gender, ethnicity, ECOG, smoking status, cancer histology, type of ICI, and PD-L1 status. No differences in types of irAEs or timing of the initial irAEs were seen. Initial irAEs were less severe in the rechallenged group, with fewer grade 3 irAEs (20% vs. 62.7%, p &lt; 0.001), no grade 4 irAEs (0% vs. 6.8%, p &lt; 0.001), less IV corticosteroid use (2.5% vs. 23.7%, p = 0.01), and less frequent hospitalizations for irAEs (7.5% vs. 42.4%, p &lt; 0.001). After rechallenging, 24 of 40 (60%) patients had recurrence of the same or de-novo irAEs. 20 (50%) developed second grade≥2 irAEs with 13 (32.5%) grade 2, and 7 (17.5%) grade 3. No grade 4 irAE or irAE-related death occurred after rechallenging. Among the 24 patients with second irAEs, 6 (25%) still had residual grade 1 irAEs upon rechallenging, while none of the 16 patients without second irAEs had residual irAEs (p = 0.03). With a median follow-up of 572 days, no statistically significant differences in overall survival (p = 0.67, HR 1.15 with 95% CI 0.60-2.22) or PFS (p = 0.57, HR 0.83 with 95% CI 0.43-1.59) were noted between the two groups, which were adjusted for age, gender, ethnicity, ECOG, PD-L1 status, grade of initial irAEs, and best objective response (OR) prior to initial irAEs. Conclusions: In real-world practice, clinicians tend to rechallenge patients with less severe irAEs. Our study showed that rechallenge was associated with a relative high risk of second grade≥2 irAEs. The risk was less if the initial irAEs were resolved. The second irAEs were not more severe than the first. Rechallenge can be performed under close monitoring, ideally, after the initial irAEs have completed resolved. The survival outcomes of ICI rechallenge and discontinuation were similar. ICI discontinuation is one feasible strategy after grade≥2 irAEs, especially severe irAEs.[Table: see text]
Carcinoid syndrome and valvular heart disease: A national perspective on patient characteristics and cardiovascular outcomes.
Authors: Shivani Dalal, Krunalkumar Patel, Atif Mahmoud Hussein, Krista Isaac, Akash Patel, Boula Gattas, Misha Dalal
Journal: Journal of Clinical Oncology (2022)

e16218 Background: Carcinoid is a well differentiated neuroendocrine tumor (NET) arising most commonly in the gastrointestinal tract or bronchopulmonary system. Carcinoid syndrome is a constellation of symptoms mediated by a myriad of vasoactive substances elaborated by the Carcinoid tumor, of which serotonin is most prominent in the pathophysiology of Carcinoid heart disease (CHD). CHD is characterized by pathognomonic plaque-like deposits of fibrous tissue on the endocardium of valvular cusps, leaflets, papillary muscles and cords. Clinical manifestations include valvular heart disease(VHD), arrhythmias and coronary heart disease. We aim to determine the impact of co-existing VHD in patients with CHD on morbidity, mortality, length of stay and mean hospitalization costs as compared to patients without coexisting VHD. Methods: We identified hospitalized adult patients with Carcinoid syndrome and divided them into patients with and without VHD from October 2015 to December 2018 from the National Inpatient Sample Database using ICD 10 Codes. We further determined demographics, baseline characteristics, associated comorbidities, mortality, length of stay (LOS) and hospitalization costs among patients with carcinoid syndrome with and without documented VHD. SAS 9.4 software was used for statistical analysis. Results: We captured 10,135 patients hospitalized with carcinoid syndrome, amongst which 705 patients were found to have VHD. The group with VHD were predominantly males (51.8 vs 48.2%), had a higher prevalence of CAD (26.2 vs 16.8%), heart failure with reduced ejection fraction(17.7 vs 3.7%), heart failure with preserved ejection fraction (13.5 vs 6%), atrial fibrillation (28.4 vs 15.3%), pleural effusion (13.5 vs 7.1%), pericardial effusion (2.8 vs 1%) as compared with patients without VHD. They were also noted to have higher inpatient mortality (9.2 vs 5.2%), length of stay (8.8 vs 6.6 days) and mean hospitalization cost (31973 vs 17734$). In the cohort with CHD and co-existing VHD, we noted mortality was highest amongst patients with involvement of pulmonary valve (13.5%) followed by tricuspid, mitral and aortic valves(13%, 8.3% and 4% respectively). Conclusions: Carcinoid tumor involves the heart in about 60% of the patients and is associated with poor long-term prognosis and is a major cause of morbidity and mortality. With mounting epidemiological evidence of poor outcomes in patients with carcinoid syndrome and VHD, our study shines light on the importance of a concerted effort to develop an algorithm for early screening, diagnosis and treatment of CHD. This necessitates multidisciplinary approach control of progressive heart failure, treatment of systemic malignancy and surgical correction of right sided valvular heart disease by utilizing services of a team consisting of surgeons, oncologists and cardiologists to guide management.
Updates in the Treatment of Patients With Colorectal Cancer
Authors: Smitha S. Krishnamurthi
Journal: Journal of the National Comprehensive Cancer Network (2022)

Abstract A number of assays are now available to estimate the prognosis of early-stage colorectal cancer, including multigene assays, the Immunoscore, and circulating tumor DNA (ctDNA). Although the results of these assays may provide prognostic information regarding the risk for recurrence, their use as a predictive assay has not yet been validated. Therefore, although these assays may be useful for prognostication, further validation would be required to include in the NCCN Guidelines. For the treatment of metastatic colorectal cancer, major advances have included the use of checkpoint inhibition in metastatic disease. Studies are currently underway to further define their optimal use.
Novel ways to fund cost-efficiency studies of expensive drugs: Efforts to maintain sustainable healthcare expenditure in the Netherlands.
Authors: Sahar Barjesteh van Waalwijk van Doorn-Khosrovani, Silvia van der Flier, Denise van den Berg
Journal: Journal of Clinical Oncology (2022)

e18831 Background: The rising costs of new cancer drugs is a major burden for healthcare system. Healthcare providers and payers constantly look for solutions to reduce inefficient use of these drugs. Methods: These solutions may involve dose-rounding, dose-banding or vial-sharing to minimise the quantity of discarded pharmaceuticals. Alternative dosing strategies, such as tapering and/or increasing the dose-interval, shortening treatment duration, or boosting potency of the drugs may also be applied. Another approach is the development of predictive/monitoring biomarkers that can prevent mis-prescribing and overuse of therapies to patients who will not benefit from such a therapy. Provided that the therapeutic benefit is retained, a lower drug exposure evidently not only results in savings for the national healthcare budget but may also limit (off-target) toxicity, reduce hospitalisation and improve quality-of-life for patients. Results: Once compelling evidence of non-inferiority is available, the roll-out one of the strategies mentioned above is justified. Parties providing financial support for cost-efficiency initiatives are then often eager to support implementation and generate potential shared savings. However, when (additional) research is required to generate adequate evidence, fund raising and finding support can be quite challenging. In the Netherlands a dedicated national fund was recently established. Treatmeds, a foundation under Dutch law, is tasked to support cost-efficiency studies and to secure and manage (part of) the funding needed for those initiatives. Treatmeds is backed by Dutch healthcare insurers. Its governance provides for decisions based on the advice of an independent Scientific Advisory Board, an Intervention Board and a Financial Board. The Scientific Advisory Board aides with selecting studies for support on a pure scientific basis, the Intervention Board considers aspects as efficiency, the possibility of reimbursement under the Dutch compulsory healthcare insurance, the cost-benefit ratio of a study and the Financial Board ultimately decides on the financial aspects of supporting a study. Although Treatmeds only has just started its activities, it is expected that it can have a pivotal role in acceleration of efficiency tools in clinical practice. Conclusions: From our own experience we can state that a dedicated national fund supporting research on improved efficiency and quality of care can be of great value to accelerate study start-up and roll-out.
Changes in cancer mortality by race and ethnicity following the Affordable Care Act implementation in California.
Authors: Elena Martinez, Scarlett Lin Gomez, Alison J. Canchola, Debora Oh, James Don Murphy, Winta Tsegay Mehtsun, K. Robin Yabroff, Matthew P. Banegas
Journal: Journal of Clinical Oncology (2022)

1500 Background: Implementation of the Affordable Care Act (ACA) has resulted in improvements in cancer outcomes but the extent to which these apply to specific racial and ethnic populations is unknown. We examined changes in health insurance distributions pre- and post-ACA and assessed cancer-specific mortality rates by race and ethnicity. Methods: The population included 167,181 newly diagnosed breast (n = 117,738), colorectal (n = 38,334), and cervix cancer (n = 11,109) patients younger than 65 years and 141,026 patients 65 years or older in the California Cancer Registry. Hazard rate ratios (HRRs) and 95% confidence intervals (CIs) were calculated using multivariable Cox regression to estimate associations with risk of 5-year cancer-specific death for each cancer site pre- (2007-2010) and post-ACA (2014-2017), and by race and ethnicity (American Indian/Alaska Natives, AIAN; Asian Americans; Hispanics; Native Hawaiian/Pacific Islanders, NHPI; non-Hispanic Blacks, NHB; and non-Hispanic whites, NHW). Difference-in-difference analysis was conducted to compare changes over time between younger (&lt; 65 years) and older (65 years and older) patients. Results: Cancer-specific mortality for patients age &lt; 65 was significantly lower post- vs. pre-ACA for colorectal cancer among Hispanic (HRR = 0.83; 95% CI: 0.74-0.93), NHB (HRR = 0.69; 95% CI: 0.58-0.81), and NHW (HRR = 0.90 95% CI: 0.84-0.97) but not Asian American (HRR = 0.95; 95% CI: 0.82-1.10) patients. The HRR for younger NHB colorectal cancer patients was significantly lower than that for patients 65 years of and older (HRR = 1.09; 95% CI, 0.95-1.25, p-interaction &lt; 0.0001). A significantly lower risk of dying from cervix cancer was observed in the post- vs. pre-ACA period among younger NHB women (HRR = 0.68; 95% CI: 0.47-0.99), but this was not significantly different than that for older women (HRR = 0.41; 95% CI, 0.16-1.01, p-interaction = 0.30). No significant differences in breast cancer-specific mortality were observed for any racial or ethnic group. Conclusions: Findings show decreases in cancer-specific mortality for colorectal and cervix cancers for some racial and ethnic groups following ACA implementation in California. These results shed light on ongoing discussions as additional states consider Medicaid expansion. Future studies should assess shifts between health insurance plans resulting from the economic impact of the 2019 novel coronavirus (COVID-19) pandemic.
Single-cell transcriptomics of adult macaque hippocampus reveals neural precursor cell populations
Authors: Zhao-Zhe Hao, Jia-Ru Wei, Dongchang Xiao, Ruifeng Liu, Nana Xu, Lei Tang, Mengyao Huang, Yuhui Shen, Changsheng Xing, Wanjing Huang, Xialin Liu, Mengqing Xiang, Yizhi Liu, Zhichao Miao, Sheng Liu
Journal: Nature Neuroscience (2022)